• Article |

    RNA sensing-mediated payload expression provides a specific, versatile, simple and generalizable means of detecting and manipulating animal cells with broad potential applications.

    • Yongjun Qian
    • , Jiayun Li
    •  & Z. Josh Huang
  • Article |

    The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.

    • Swagat Ray
    • , Arwa A. Abugable
    •  & Sherif F. El-Khamisy
  • Article |

    CDK11 associates with SF3B1 and phosphorylates threonine residues at the N terminus of SF3B1 during spliceosome activation, and the inhibition of CDK11 blocks the activation and leads to widespread intron retention and the accumulation of non-functional spliceosomes on pre-mRNAs and chromatin.

    • Milan Hluchý
    • , Pavla Gajdušková
    •  & Dalibor Blazek
  • Article |

    The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

    • Christoph Neumayr
    • , Vanja Haberle
    •  & Alexander Stark
  • Article |

    A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.

    • Drew T. Bergman
    • , Thouis R. Jones
    •  & Jesse M. Engreitz
  • Article |

    Characterization of Gibbin, encoded by AHDC1, offers insights into the epidermal and mesodermal patterning phenotypes seen in Xia–Gibbs and related syndromes in humans, which derive from abnormal mesoderm maturation as a result of gene-specific DNA methylation decisions.

    • Ann Collier
    • , Angela Liu
    •  & Anthony E. Oro
  • Article |

    In Drosophila, there are extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases.

    • Michal Levo
    • , João Raimundo
    •  & Michael S. Levine
  • Article
    | Open Access

    A study maps neuronal genomic targets of oestrogen receptor-α and shows how they coordinate brain sexual differentiation, concluding that the genome remains responsive to hormonal changes after structural dimorphisms have been established.

    • B. Gegenhuber
    • , M. V. Wu
    •  & J. Tollkuhn
  • Article
    | Open Access

    The transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship, and enhancer strength determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation.

    • Jessica Zuin
    • , Gregory Roth
    •  & Luca Giorgetti
  • Article |

    Integrated structure–function studies show that transcription-coupled DNA repair (TCR)—rather than global genomic repair—is responsible for most chromosomal repair events in bacteria, and that TCR mainly occurs independently of the Mfd translocase.

    • Binod K. Bharati
    • , Manjunath Gowder
    •  & Evgeny Nudler
  • Article
    | Open Access

    The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.

    • Goran Kokic
    • , Felix R. Wagner
    •  & Patrick Cramer
  • Article |

    BANP is identified as the transcription factor that binds the CGCG element in a DNA-methylation-dependent manner, opens chromatin and activates a class of essential CpG-island-regulated genes.

    • Ralph S. Grand
    • , Lukas Burger
    •  & Dirk Schübeler
  • Article |

    Disruption of a promoter can release its partner enhancer to activate other promoters in the same contact domain, and this process, named ‘enhancer release and retargeting’, can often lead to gene alterations that cause disease.

    • Soohwan Oh
    • , Jiaofang Shao
    •  & Michael G. Rosenfeld
  • Article |

    A ChIP–exo method is used to define the genome-wide positional organization of proteins associated with gene transcription, DNA replication, centromeres, subtelomeres and transposons, revealing distinct protein assemblies for constitutive and inducible gene expression.

    • Matthew J. Rossi
    • , Prashant K. Kuntala
    •  & B. Franklin Pugh
  • Article |

    An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

    • Jian Yan
    • , Yunjiang Qiu
    •  & Bing Ren
  • Article |

    Inhibitors of mitochondrial transcription that target human mitochondrial RNA polymerase provide a chemical biology tool for studying the role of mitochondrial DNA expression in a wide range of pathologies.

    • Nina A. Bonekamp
    • , Bradley Peter
    •  & Nils-Göran Larsson
  • Article |

    The RNA polymerase from the crAss-like bacteriophage phi14:2, which is translocated into the host cell with phage DNA and transcribes early phage genes, is structurally most similar to eukaryotic RNA interference polymerases, suggesting that the latter have a phage origin.

    • Arina V. Drobysheva
    • , Sofia A. Panafidina
    •  & Maria L. Sokolova
  • Article |

    During the activation of mouse macrophages by lipopolysaccharides, histone deacetylase 3 controls inflammatory responses by both repressing and activating gene transcription depending on its differential association with transcription factors.

    • Hoang C. B. Nguyen
    • , Marine Adlanmerini
    •  & Mitchell A. Lazar
  • Article |

    The chromatin protein MeCP2 is a component of dynamic, liquid-like heterochromatin condensates, and the ability of MeCP2 to form condensates is disrupted by mutations in the MECP2 gene that occur in the neurodevelopmental disorder Rett syndrome.

    • Charles H. Li
    • , Eliot L. Coffey
    •  & Richard A. Young
  • Article |

    RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.

    • Karan J. Abraham
    • , Negin Khosraviani
    •  & Karim Mekhail
  • Article |

    Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.

    • Justin C. Wheat
    • , Yehonatan Sella
    •  & Ulrich Steidl
  • Article |

    A cryo-electron microscopy structure of the RNA-dependent RNA polymerase of SARS-CoV-2 sheds light on coronavirus replication and enables the analysis of the inhibitory mechanisms of candidate antiviral drugs.

    • Hauke S. Hillen
    • , Goran Kokic
    •  & Patrick Cramer
  • Article |

    Cryo-electron microscopy structures of the DNA-binding domains of the pioneer transcription factor SOX2 and its close homologue SOX11 elucidate the role of these factors in initiating chromatin opening and nucleosome remodelling.

    • Svetlana O. Dodonova
    • , Fangjie Zhu
    •  & Patrick Cramer
  • Article |

    The authors provide high-resolution structures of two arenavirus polymerases, revealing that the active site of arenavirus polymerase is inherently switched on, without the requirement for allosteric activation by 5′-viral RNA, and that dimerization facilitates polymerase activity.

    • Ruchao Peng
    • , Xin Xu
    •  & Yi Shi
  • Article |

    Long noncoding RNAs and certain unstable transcripts tend to localize to chromatin, in a process that is shown here to depend on an RNA motif that recognizes the small nuclear ribonuclear protein U1, and to rely on transcription.

    • Yafei Yin
    • , J. Yuyang Lu
    •  & Xiaohua Shen
  • Article |

    The cryo-electron microscopy structure of the 16-subunit yeast SWI/SNF complex RSC in complex with a nucleosome substrate provides insights into the chromatin-remodelling function of this family of protein complexes.

    • Felix R. Wagner
    • , Christian Dienemann
    •  & Patrick Cramer
  • Article |

    Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

    • Gabor Papai
    • , Alexandre Frechard
    •  & Adam Ben-Shem
  • Article |

    Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

    • Haibo Wang
    • , Christian Dienemann
    •  & Patrick Cramer
  • Article |

    The topoisomerase Top2 and the chromatin-binding protein Hmo1 maintain under-wound and over-wound DNA at different regions within a gene and thereby modulate the topology of genes.

    • Yathish Jagadheesh Achar
    • , Mohamood Adhil
    •  & Marco Foiani
  • Article |

    ERK reversibly regulates embryonic stem cell transcription via selective redistribution of co-factors and RNA polymerase from pluripotency to early differentiation enhancers, while leaving transcription factors bound to their enhancers, thus preserving plasticity.

    • William B. Hamilton
    • , Yaron Mosesson
    •  & Joshua M. Brickman
  • Review Article |

    Structural and microscopy studies of gene transcription underpin a model in which phosphorylation controls the shuttling of RNA polymerase II between promoter and gene-body condensates to regulate transcription initiation and elongation.

    • Patrick Cramer
  • Letter |

    A screen of 23 transcriptional cofactors for their ability to activate 72,000 candidate core promoters in Drosophila melanogaster identified distinct compatibility groups, providing insight into mechanisms that underlie the selective activation of transcriptional programs.

    • Vanja Haberle
    • , Cosmas D. Arnold
    •  & Alexander Stark
  • Article |

    Transcriptional adaptation, a genetic compensation process by which organisms respond to mutations by upregulating related genes, is triggered by mRNA decay and involves a sequence-dependent mechanism.

    • Mohamed A. El-Brolosy
    • , Zacharias Kontarakis
    •  & Didier Y. R. Stainier